ABSTRACT
The bark of Ulmus davidiana var. japonica Nakai (Ulmaceae) has been used in traditional Korean medicine for chronic inflammation in the gastrointestinal tract. Here we investigated the frequency and cytokine profile of the major immune cells in the small intestinal lamina propria (SI LP), spleen, and mesenteric lymph nodes (MLNs) of mice treated orally with Ulmus davidiana var. japonica Nakai bark water extract (UDE) to address the immunomodulatory role of this herb in intestinal homeostasis. B6 mice were given 5g/kg UDE once daily for 14 days. They were then sacrificed, and cells were isolated from the spleen, MLNs, and SI LP. The proportion of B versus T lymphocytes, CD4(+) versus CD8(+) T lymphocytes, Th1 and Th17 cells, and Foxp3(+) regulatory T cells in the spleen, MLNs, and SI LP were analyzed. The frequency of antigen-presenting cells (APCs), including dendritic cells, macrophages, and eosinophils in the SI LP and the expression of costimulatory molecules on APCs were also evaluated. The numbers and frequencies of Th1 and Th17 cells in the SI LP were significantly reduced in the UDE-treated mice compared with PBS controls. In addition, the proportion of IL-4-producing eosinophils in the SI LP was significantly elevated in the UDE-treated mice compared with controls. Taken together, these data indicate that UDE up-regulates the number and frequency of SI LP eosinophils, which can down-regulate the Th1 and Th17 responses via IL-4 secretion and contribute to intestinal homeostasis.
Subject(s)
Eosinophils/drug effects , Intestine, Small/drug effects , Plant Extracts/pharmacology , Th1 Cells/drug effects , Th17 Cells/drug effects , Ulmus/chemistry , Administration, Oral , Animals , Antigen-Presenting Cells/drug effects , Antigen-Presenting Cells/immunology , Antigen-Presenting Cells/metabolism , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Cell Count , Enzyme-Linked Immunosorbent Assay , Eosinophils/immunology , Eosinophils/metabolism , Female , Homeostasis/drug effects , Homeostasis/immunology , Immunoglobulin E/blood , Immunoglobulin E/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Interleukin-4/immunology , Interleukin-4/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestine, Small/immunology , Intestine, Small/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Plant Bark/chemistry , Plant Extracts/administration & dosage , Plant Extracts/immunology , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Up-Regulation/drug effectsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Cho-kyung-jong-ok-tang (CKJOT) is a traditional Korean herbal formula specifically used for female infertility including unexplained recurrent pregnancy loss (RPL). AIM OF THE STUDY: The present study aims to evaluate the effects of CKJOT on mouse natural killer (NK) cells to address the possible immunological basis of protective effects of this herbal medicine on unexplained RPL. MATERIALS AND METHODS: NK cells isolated from spleens of 6-week-old C57BL/6 mice were differentiated into NK0, NK1, and NK2 cells in the presence of various concentrations of CKJOT-extract. Apoptotic cell number, level of intracellular cytokines, and expression of cytokine-related transcription factors were measured. RESULTS: CKJOT had little effect in improving viability of NK0, NK1, and NK2 cells. However, CKJOT addition during NK cell differentiation suppressed the production of interferon-gamma (IFN-γ), and enhanced that of interleukin-5, in the NK1 and NK2 subsets, respectively. T-bet, a transcription factor associated with IFN-γ expression was down-regulated; while Th2 linked transcription factors (STAT6 and GATA3) were up-regulated especially with 100 µg/mL treatment of CKJOT. CONCLUSION: The type 2 shift in NK cell-secreted cytokines induced by CKJOT in mouse NK cells may explain the protective effect associated with its traditional use in unexplained RPL.
Subject(s)
Abortion, Habitual/prevention & control , Interferon-gamma/biosynthesis , Interleukin-5/biosynthesis , Killer Cells, Natural/metabolism , Medicine, Korean Traditional , Phytotherapy , Th2 Cells/physiology , Abortion, Habitual/immunology , Animals , Cell Differentiation/drug effects , Cell Differentiation/immunology , Cell Survival/drug effects , GATA3 Transcription Factor/metabolism , Killer Cells, Natural/drug effects , Mice , Mice, Inbred C57BL , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , STAT6 Transcription Factor/metabolism , Spleen/cytology , T-Box Domain Proteins/metabolismABSTRACT
AIM OF STUDY: This study was performed to elicit the effectiveness of bee venom (BV), a traditional immunosuppressive Korean acupuncture agent, on the maturation of dendrtic cells (DCs). MATERIALS AND METHODS: Immature dendritic cells (iDCs) were generated from mouse bone marrow cells with GM-CSF. After 10 days of initial differentiation, DCs were activated with lipopolysaccharides (LPS) for another 48h in the presence or absence of BV. Surface molecule analysis, intracytoplasmic staining of cytokines, FITC-conjugated antigen uptake, and transwell migration assays were conducted with iDCs and activated DCs. RESULTS: Up-regulation of costimulatory molecules, typical of mature DCs (mDCs) was inhibited by addition of BV. Pro-inflammatory cytokines were also found to be reduced with BV treatment in LPS-stimulated DC. A decrease in antigen uptake upon the maturation of DC was reversed in low dose BV treated mDC. In addition, BV treated mDC demonstrated reduced directional migration in response to CCL21, a lymphoid chemokine which directs mDC. CONCLUSIONS: BV may have a therapeutic effect an on abnormally activated immune status, such as autoimmune rheumatoid arthritis, through an immune-modulatory effect on DC.